Dermatotoxicologic clinical solutions: hair dying in hair dye allergic patients?

This article describes how to identify allergic contact dermatitis resulting from hair dye, and outlines interventions and prevention principles for those who wish to continue dyeing their hair despite being allergic. Hair dye chemicals thought to be the most frequent sensitizers are discussed with instructions for health care providers on how to counsel patients about techniques to minimize exposure to allergenic substances. This framework should allow many patients to continue dyeing their hair without experiencing adverse side effects.     

γ-Hydroxybutyrate (GHB)-induced respiratory depression: combined receptor-transporter inhibition therapy for treatment in GHB overdose

Overdose of γ-hydroxybutyrate (GHB) frequently causes respiratory depression, occasionally resulting in death; however, little is known about the dose-response relationship or effects of potential overdose treatment strategies on GHB-induced respiratory depression. In these studies, the parameters of respiratory rate, tidal volume, and minute volume were measured using whole-body plethysmography in rats administered GHB. Intravenous doses of 200, 600, and 1500 mg/kg were administered to assess the dose-dependent effects of GHB on respiration. To determine the receptors involved in GHB-induced respiratory depression, a specific GABA(B) receptor antagonist, (2S)-(+)-5,5-dimethyl-2-morpholineacetic acid (SCH50911), and a specific GABA(A) receptor antagonist, bicuculline, were administered before GHB. The potential therapeutic strategies of receptor inhibition and monocarboxylate transporter (MCT) inhibition were assessed by inhibitor administration 5 min after GHB. The primary effect of GHB on respiration was a dose-dependent decrease in respiratory rate, accompanied by an increase in tidal volume, resulting in little change in minute volume. Pretreatment with 150 mg/kg SCH50911 completely prevented the decrease in respiratory rate, indicating agonism at GABA(B) receptors to be primarily responsible for GHB-induced respiratory depression. Administration of 50 mg/kg SCH50911 after GHB completely reversed the decrease in respiratory rate; lower doses had partial effects. Administration of the MCT inhibitor l-lactate increased GHB renal and total clearance, also improving respiratory rate. Administration of 5 mg/kg SCH50911 plus l-lactate further improved respiratory rate compared with the same dose of either agent alone, indicating that GABA(B) and MCT inhibitors, alone and in combination, represent potential treatment options for GHB-induced respiratory depression.     

Accumulation of β-agonists clenbuterol and salbutamol in black and white mouse hair

Hair has been shown to be an excellent site for the accumulation of different drugs including β-agonists, and therefore, it would be an appropriate matrix for surveillance for the presence of drug residues. The aim of this study was to determine concentrations and to compare accumulation of two different β-agonists in black and white mice hair by use of ELISA as a screening quantitative method. The study included 200 8-week-old white and black mice. One group of black mice and one group of white mice were treated with clenbuterol in a dose of 2.5 mg/kg body mass per os for 28 days. Other animals were treated in the same way with salbutamol. The highest (±SD) clenbuterol concentration of 631.4 ± 23.5 ng/g in black hair and 228.5 ± 156.2 ng/g in white hair was determined on day 1 of treatment withdrawal. Study results revealed the black-to-white hair ratio of clenbuterol accumulation to be 1:2-1:4 and of salbutamol accumulation 1:1.4. The mean (±SD) salbutamol concentrations determined on day 1 of treatment withdrawal was 23.9 ± 0.9 ng/g and 16.4 ± 1.1 ng/g in black and white hair samples, respectively. The study demonstrated that residues could be determined in hair samples even after a 30-day withdrawal period.     

Pharmacokinetic properties of γ-hydroxybutyrate (GHB) in whole blood, serum, and urine

Over the last 10-15 years, γ-hydroxybutyrate (GHB) and γ-butyrolactone have become increasingly popular "club drugs", but they have also gained attention as potential agents of drug-facilitated sexual assault (DFSA). Several studies have attempted to characterize GHB's pharmacokinetic properties in humans, and the aim of this paper is to build on this research with an emphasis on DFSA cases. A 25 mg/kg dose of GHB was given to 12 GHB-na?ve volunteers (6 men and 6 women). Urine and blood samples (serum and whole blood) were collected and analyzed by gas chromatography-mass spectrometry following liquid-liquid extraction. The urinary T(max) was 1 h in 11 volunteers with a mean C(max) of 67.6 mg/L (32.6-161.3 mg/L). Urinary concentrations rapidly decreased to < 10 mg/L (interpretive limit) for 11 volunteers after just 4 h. Data derived from whole blood (mean C(max) = 48.0 mg/L, T(max) = 24.6 min) closely matched that from serum (mean C(max) = 59.4 mg/L, T(max) = 23.3 min), suggesting GHB is distributed into erythrocytes. All 12 volunteers had GHB concentrations of less than 5 mg/L in both whole blood and serum after 3 h. Results verify the rapid elimination of GHB and the limited retrospective power of a concentration-based approach to prove GHB administration in blood and urine and confirm that, in DFSA cases, samples should be collected as soon as possible.     

The safety,stability, and compatibility of fragrances in skin and hair products†

Abstract

The efforts of the formulating chemist, perfumer, and toxicologist represent the creative forces that ultimately merge to accomplish a finished formulation. Because the ingredients in a compounded fragrance are proprietary to the company that produces them, the formulating chemist must add a mixture of unknown substances to his basic formulation with the hope that they will be compatible in functionality, stability, and safety. A well-controlled stability and safety testing program is needed to assure complete compatibility between the base formulation and the fragrance.

Potential stability problems include changes in viscosity, color, odor, clarity of transparent systems, and emulsion stability. These changes may be caused by hydrolysis, oxidation, reaction to light, reaction to metals, insolubilities, reaction to processing conditions, and packaging materials. The interactions which occur during these changes can cause the formation of new materials that may have irritation or sensitization potential. We recommend that samples of product that have successfully passed shelf-life testing be furnished to the toxicologist for a complete battery of safety tests, including controlled use testing. This procedure should help to assure that untoward reactions do not occur during consumer use.     

Sedative and hypothermic effects of γ-hydroxybutyrate (GHB) in rats alone and in combination with other drugs: Assessment using biotelemetry

The recreational drug γ-hydroxybutyrate (GHB) has euphoric effects and can induce sedation and body temperature changes. GHB is frequently combined with other recreational drugs although these interactions are not well characterised. The present study used biotelemetry to provide a fine-grained analysis of the effects of GHB on body temperature and locomotor activity in freely moving rats, and investigated interactions between GHB and 3,4-methylenedioxymethamphetamine (MDMA), methamphetamine (METH) and various antagonist drugs. GHB (1000 mg/kg) caused profound sedation for more than 2 h and a complex triphasic effect on body temperature: an initial hypothermia (5–40 min), followed by hyperthermia (40–140 min), followed again by hypothermia (140–360 min). A lower GHB dose (500 mg/kg) also caused sedation but only a hypothermic effect that lasted up to 6 h. The dopamine D₁ receptor antagonist SCH 23390 (1 mg/kg), the opioid antagonist naltrexone (1 mg/kg), the benzodiazepine antagonist flumazenil (10 mg/kg), and the 5-HT_2A/2C receptor antagonist ritanserin (1 mg/kg) did not prevent the overall sedative or body temperature effects of GHB (1000 mg/kg). However the GABA_B antagonist SCH 50911 (50 mg/kg) prevented the hyperthermia induced by GHB (1000 mg/kg). Repeated daily administration of GHB (1000 mg/kg) produced tolerance to the sedative and hyperthermic effects of the drug and cross-tolerance to the sedative effects of the GABA_B receptor agonist baclofen (10 mg/kg). A high ambient temperature of 28 °C prevented the hypothermia obtained with GHB (500 mg/kg) at 20 °C, while GHB (500 mg/kg) reduced the hyperthermia and hyperactivity produced by co-administered doses of MDMA (5 mg/kg) or METH (1 mg/kg) at 28 °C. These results further confirm a role for GABA_B receptors in the hypothermic and sedative effects of GHB and show an interaction between GHB and MDMA, and GHB and METH, that may be relevant to the experience of recreational users who mix these drugs.     

Are cannabinoids detected in hair after washing with Cannabio shampoo?

Today, cannabis plants are used in shampoo preparations, in foodstuffs (e.g., oils, noodles, crackers, etc.), and in beverages (e.g., tea). These products often contain < 1% delta9-tetrahydrocannabinol (THC) in order to eliminate psychoactive effects, but some of them can include 1 to 3% of THC. Gas chromatography-mass spectrometry (GC-MS) analysis of Cannabio shampoo revealed the presence of THC (412 ng/mL) and two constituents of cannabis plants, cannabidiol (CBD, 4079 ng/mL) and cannabinol (CBN, 380 ng/mL). In order to verify if normal hygiene practices with Cannabio shampoo can result in positive tests for cannabinoids in hair, three subjects washed their hair with this shampoo once daily for two weeks. After this period, hair specimens were collected. In the three hair specimens, THC, CBD, and CBN were never detected within their limits of detection, 0.05, 0.02, and 0.01 ng/mg, respectively. We concluded that the use of Cannabio shampoo during normal hygiene practices cannot be considered as a source of potential contamination of hair. In a second experiment, drug-free hair specimens (200 mg) were incubated in 10 mL water/Cannabio shampoo (20:1, v/v) for 30 min, 2 h, and 5 h. After incubation, hair strands were washed with water and separated into two portions. One portion was extracted directly; the second was decontaminated with methylene chloride and then extracted. After an incubation period of 30 min, the analysis of hair by GC-MS did not reveal the presence of THC, CBD, and CBN in hair, regardless of whether the hair was decontaminated. After an incubation period of 2 h, specimens tested positive for CBD (0.11 ng/mg without decontamination and 0.10 ng/mg with decontamination) and CBN (0.02 ng/mg without decontamination and 0.02 ng/mg after decontamination). After an incubation period of 5 h, specimens tested positive for CBD (0.25 ng/mg without decontamination and 0.14 ng/mg after decontamination) and CBN (0.02 ng/mg without decontamination and 0.02 ng/mg after decontamination). In all cases, THC was never detected. Extensive but unrealistic use of Cannabio shampoo can cause drug-free hair to test positive for CBD and CBN but not for the primary psychoactive drug THC.     

Quantification of cannabinoids in human hair using a modified derivatization procedure and liquid chromatography–tandem mass spectrometry

The aim of this work was to develop and validate a liquid chromatography–tandem mass spectrometry method for detecting of the main cannabinoids, cannabinol (CBN) and tetrahydrocannabinol (THC) and the primary metabolite 11-nor-9-carboxy-Δ⁹-tetrahydrocannabinol (THC-COOH) in hair samples. Extraction of the cannabinoids was carried out by a polymeric strong anion mixed-mode solid-phase extraction cartridge and then employing methanolic HCl followed by 2-fluoro-1-methylpyridinium-p-toluenesulfonate (FMP-TS) as a derivatization procedure of carboxyl and phenolic groups, respectively, offering enhanced sensitivity for the detection of THC-COOH in hair matrices. Formation of a methyl ester increased its lipophilicity and removed the negative charge on the carboxyl group. Calibration curves were prepared over the range of 0.02–4 pg/mg of hair for THC and CBN and 0.2–12 pg/mg of hair for THC-COOH. The extraction recovery was between 81% and 105% for all compounds. The limit of detection (LOD) and limit of quantification (LOQ) were 2 and 20 pg/mg, respectively, for both CBN and THC and 0.1 and 0.2 pg/mg, respectively, for THC-COOH, which met the society of hair testing recommendation. Intra-assay and interassay precision were always lower than 4% and 11%, respectively for these cannabinoids, whereas intra-assay and interassay bias were between +14% and −18% and +15% and −12%, respectively. Twenty-seven hair specimens from cannabis users were investigated. The concentrations of CBN, THC and THC-COOH gave ranges of (0.022–2.562 ng/mg), (0.049–0.431 ng/mg) and (0.222–4.867 pg/mg), respectively. This new method of derivatization improves the LOD to ensure detection of the metabolite.     

In‐vitro permeation of drugs into porcine hair follicles: is it quantitatively equivalent to permeation into human hair follicles?

It is already well-established that the general permeability properties of porcine skin are close to those of human skin. However, very little is known with respect to drug absorption into hair follicles and the similarities if any between the two types of tissue. The aim of this study was to use the skin sandwich system to quantify follicular drug absorption into porcine hair follicles. To our knowledge, this is the first time that the skin sandwich has been extended to porcine tissue. For this purpose, seven different drugs -- estradiol, corticosterone, hydrocortisone, aldosterone, cimetidine, deoxyadenosine and adenosine -- exhibiting a wide range of log octanol-water partition coefficients (log K(o/w)), but comparable molecular weights, were chosen as candidate solutes. The results showed a parabolic profile with maximal follicular contribution occurring at intermediate log K(o/w) values. Linear regression analysis indicated that the follicular contributions in porcine skin correlated well with previously published follicular contributions in human skin (r(2) = 0.87). The novelty of this research is that we show that porcine tissue is a good surrogate for modelling human skin permeability within the specific context of quantifying drug absorption into hair follicles.     

LC–MS/MS method for quantification of baclofen in hair: A useful tool to assess compliance in alcohol dependent patients?

To evaluate adherence to treatment, we developed and validated a novel liquid chromatography–tandem mass spectrometry (LC–MS/MS) method for baclofen quantification in hair.Twenty mg was washed twice with dichloromethane, incubated in phosphate buffer (pH 5) for 10 minutes at 95°C, then extracted by liquid‐liquid extraction in alkaline condition. Baclofen‐d₄ was used as the internal standard. This method was applied to assess compliance in4 treated alcohol‐dependent patients (3 dead and one living). Blood quantification of baclofen and ethanol were performed in the 4 cases. Hair ethylglucuronide (ethanol metabolite, EtG) measurement (2x3 cm) was associated in 1 patient. Baclofen quantification in hair was validated over the range 10–5000 pg/mg. The accuracy was within 96.0%–110.9% and the precision was less than 9.3%. Baclofen segmental (3x2cm) hair concentrations found in the living patient were 4420, 4260, and 4380 pg/mg, reflecting a regular exposure over the last 6 months and suggesting patient compliance. However, the high EtG level found in this patient in the analyzed segments (225 pg/mg and 215 pg/mg) showed excessive alcohol consumption during the same period, suggesting therapeutic failure. In the 3 deceased patients, the non‐segmental analysis of hair showed baclofen concentrations of 15, 545, and 2475 pg/mg. The low concentrations in the 2 first cases are compatible either with a poor compliance or to a beginning of a treatment. This is the first measurement of baclofen in hair of alcohol dependent patients. It could be used as a monitoring biomarker to assess patient's compliance.     

The nicotinic receptor of cochlear hair cells: A possible pharmacotherapeutic target?

Mechanosensory hair cells of the organ of Corti transmit information regarding sound to the central nervous system by way of peripheral afferent neurons. In return, the central nervous system provides feedback and modulates the afferent stream of information through efferent neurons. The medial olivocochlear efferent system makes direct synaptic contacts with outer hair cells and inhibits amplification brought about by the active mechanical process inherent to these cells. This feedback system offers the potential to improve the detection of signals in background noise, to selectively attend to particular signals, and to protect the periphery from damage caused by overly loud sounds. Acetylcholine released at the synapse between efferent terminals and outer hair cells activates a peculiar nicotinic cholinergic receptor subtype, the α9α10 receptor. At present no pharmacotherapeutic approaches have been designed that target this cholinergic receptor to treat pathologies of the auditory system. The potential use of α9α10 selective drugs in conditions such as noise-induced hearing loss, tinnitus and auditory processing disorders is discussed.     

How are the inner hair cells and auditory nerve fibers activated without the mediation of the outer hair cells and the cochlear amplifier?

The present study was designed to assess whether, in the presence of a depression of the cochlear amplifier i.e. a sensorineural hearing loss (SNHL), the inner hair cells (IHCs) require the presence of a normal endocochlear potential for transduction. An SNHL was induced by injecting salicylic acid (which binds to the motor protein prestin in the outer hair cells), and then furosemide (which depresses the endocochlear potential) was injected. Furosemide did not cause an additional elevation of the threshold of the auditory nerve brainstem evoked response (ABR) over that induced by the salicylic acid injection. Exposure to noise was also used to induce a SNHL in other mice, and then furosemide was injected. Here too furosemide did not cause an additional ABR threshold elevation over that induced by the noise. These results show that the IHCs (and the auditory nerve) can be excited in the presence of a SNHL (i.e. without the cochlear amplifier) and in the absence of an endocochlear potential. Possible mechanisms of excitation in such a state are discussed.     

Optical coherent tomography for in vivo determination of changes in hair cross section and diameter during treatment with glucocorticosteroids--a simple method to screen for doping substances?

Eighty percent of hair follicles are in the growing phase. They grow approximately 0.3 mm/day. The hair follicles are surrounded by a close network of capillaries, which supplies them with nutrients. It is well known that substances which influence the metabolic processes of humans also influence hair growth. Steroids, which are used for doping in sport, are among these substances. In the present paper, optical coherent tomography is used for the analysis of changes in the hair structure during the application of steroids for the treatment of patients suffering from auto-immune diseases. Significant differences in the hair cross section could be detected during treatment, while the shape of the hairs was not influenced. It could be demonstrated that optical coherence tomography is a suitable, non-invasive and low-cost measuring technique that can be applied for doping control and screening. As a result of this screening process, only those athletes who show abnormalities in hair parameters would need to be investigated by classical analytical methods. The results presented in this study are not only important for doping controls, but also for several clinical applications, such as therapy and compliance control in cases where the applied substances induce changes in the hair structure.     

Reconsidering GHB: orphan drug or new model antidepressant?

For six decades, the principal mode of action of antidepressant drugs is the inhibition of monoamine re-uptake from the synaptic cleft. Tricyclic antidepressants, selective serotonin re-uptake inhibitors (SSRIs) and the new generation of dual antidepressants all exert their antidepressant effects by this mechanism. In the early days of the monoaminergic era, other efforts have been made to ameliorate the symptoms of depression by pharmacological means. The gamma-aminobutyric acid (GABA) system was and possibly still is one of the main alternative drug targets. Gammahydroxybutyrate (GHB) was developed as an orally active GABA analogue. It was tested in animal models of depression and human studies. The effects on sleep, agitation, anhedonia and depression were promising. However, the rise of benzodiazepines and tricyclic antidepressants brought GHB out of the scope of possible treatment alternatives. GHB is a GABA(B) and GHB receptor agonist with a unique spectrum of behavioural, neuroendocrine and sleep effects, and improves daytime sleepiness in various disorders such as narcolepsy, Parkinson's disease and fibromyalgia. Although it was banned from the US market at the end of the 1990s because of its abuse and overdose potential, it later was approved for the treatment of narcolepsy. New research methods and an extended view on other neurotransmitter systems as possible treatment targets of antidepressant treatment brought GHB back to the scene. This article discusses the unique neurobiological effects of GHB, its misuse potential and possible role as a model substance for the development of novel pharmacological treatment strategies in depressive disorders.     

Mercury, pets’ and hair: baseline survey of a priority environmental pollutant using a noninvasive matrix in man’s best friend

Pet cats and dogs have been successfully used as indicators of environmental pollution by a great variety of chemicals, including metals. However, information on mercury (a well know priority environmental pollutant) concentrations in household pets tissues and/or organs is scarce. Thus, in the present work we quantified total mercury (Hg_Total) in blood and hair samples from twenty-six household dogs. The obtained results disclose relatively low levels of total mercury in the surveyed dogs, with values ranging from 0.16 to 12.38 ng g^?1 in blood; and from 24.16 to 826.30 ng g^?1 in hair. Mercury concentrations were independent of gender, age and diet type. A highly significant positive correlation was established between total mercury in blood and hair, validating the latter as a surrogate, non-invasive matrix for mercury exposure evaluation. Additionally, the obtained blood to hair ratio (200) is similar to the one described for humans reinforcing the suitability of dogs as sentinels. Overall, the determination of total mercury levels in dogs’ hair samples proved to be a good screening method for the estimation of mercury burden in this species. We propose the quantification of Hg_Total in hair as a screening method for sentinels like household pets to be performed in routine veterinary visits.     

γ-羟基丁丙酯(GHB)滥用情况简介

在美国 ,虽然被滥用的主要物质仍然是大麻、可卡因和酒精 ,但一些新的“娱乐药”也不断出现 ,γ -羟基丁丙酯（ｇａｍｍａｈｙｄｒｏｘｙｂｕｔｙｒａｔｅ ,ＧＨＢ）就是其中的一个［１］。ＧＨＢ又称“液体迷魂药”或“Ｇ”毒 ,是一种无色、无味、无嗅的中枢神经抑制剂［２］。和摇头丸一样 ,ＧＨＢ主要是青少年和青年人在夜总会、狂欢舞会等通宵舞会上使用 ,以获得轻松愉悦的感觉。ＧＨＢ滥用现象最早出现在美国９０年代初期 ,随后在其他国家也发生滥用现象。尽管ＧＨＢ是一种舞会药 ,但在下述情况下也会使用：(１)据传ＧＨＢ能够刺激生长…     

γ一羟基丁丙酯(GHB)滥用情况简介

在美国,虽然被滥用的主要物质仍然是大麻、可卡因和酒精,但一些新的"娱乐药”也不断出现,γ-羟基丁丙酯(gamma hydroxybutyrate,GHB)就是其中的一个[1].GHB又称"液体迷魂药”或"G”毒,是一种无色、无味、无嗅的中枢神经抑制剂[2].和摇头丸一样,GHB主要是青少年和青年人在夜总会、狂欢舞会等通宵舞会上使用,以获得轻松愉悦的感觉.GHB滥用现象最早出现在美国90年代初期,随后在其他国家也发生滥用现象.尽管GHB是一种舞会药,但在下述情况下也会使用:(1)据传GHB能够刺激生长激素的释放,因此不少人试图用GHB减少脂肪和增强肌肉;(2)一些酗酒者使用GHB试图治疗酒中毒或缓解对酒精的渴求,但还缺少有关的医学证据;(3)在美国试用于治疗嗜睡症,但有严格的规定.